Anti-tumor Effects of Idarubicin Hydrochloride in Desmoid Tumors.

Background/aim: Desmoid tumors (DTs), also referred to as aggressive fibromatosis, originate from connective tissues and typically manifest with a propensity for local invasion. Despite extensive research efforts aimed at exploring novel anti-tumor agents for DTs, the development of effective clinical management strategies remains an ongoing challenge due to the limited success of current treatments, which frequently lead to inconsistent outcomes and a high recurrence rate of DTs. To overcome these limitations, we focused our research aim on a drug repositioning approach to identify existing medications that could be effective against DTs.
Materials and Methods: Mouse models with Apc mutations, specifically Apc ^1638N/+ and Apc ^1638N/+ /Trp53 ^-/- , were generated to study DTs. Primary desmoid cells were isolated from these models for experimental analysis. Idarubicin hydrochloride (IDH), a topoisomerase II (TOPO II) inhibitor, was tested on these primary cells, colorectal cancer (CRC) cell lines, and tumor organoids derived from Apc ^1638N/+ mice. Cell viability was determined with the WST reagent and colony formation assay was evaluated. The anti-tumor efficacy of IDH was tested in an in vivo CRC xenograft model using HCT-116 cells.
Results: The TOPO II inhibitor IDH showed significant growth inhibition effects on Apc ^1638N/+ and Apc ^1638N/+ /Trp53 ^-/- cells. IDH also showed remarkable anti-tumor effects on CRC cell lines and tumor organoids derived from intestinal tumor cells of the Apc ^1638N/+ mouse model. Furthermore, IDH exerted dramatic anti-tumor effects on an HCT-116 cell line xenograft mouse model.
Conclusion: IDH could be a promising therapeutic agent for inhibiting DTs and CRC by targeting TOPO II.
(Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)